NM_145080.4:c.547A>G

Variant names:

• chr16-27226773-T-C
• rs2083700612
• NM_145080.4:c.547A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145080.4(NSMCE1):​c.547A>G​(p.Thr183Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T183M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NSMCE1 NM_145080.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.766
• Publications: 0 publications found

Genes affected

NSMCE1 (HGNC:29897): (NSE1 homolog, SMC5-SMC6 complex component) Enables protein dimerization activity and ubiquitin protein ligase activity. Involved in positive regulation of response to DNA damage stimulus. Located in nucleoplasm. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110321015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMCE1	NM_145080.4	MANE Select	c.547A>G	p.Thr183Ala	missense	Exon 6 of 8	NP_659547.2	Q8WV22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSMCE1	ENST00000361439.9	TSL:1 MANE Select	c.547A>G	p.Thr183Ala	missense	Exon 6 of 8	ENSP00000355077.4	Q8WV22
	NSMCE1	ENST00000869101.1		c.679A>G	p.Thr227Ala	missense	Exon 7 of 9	ENSP00000539160.1
	NSMCE1	ENST00000869102.1		c.610A>G	p.Thr204Ala	missense	Exon 7 of 9	ENSP00000539161.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.77
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Benign	0.33	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.34		Loss of phosphorylation at T183 (P = 0.0766)
MVP		0.87
MPC		0.39
ClinPred		0.082	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2083700612; hg19: chr16-27238094;